ID   G6PC3_MOUSE             Reviewed;         346 AA.
AC   Q6NSQ9; Q3TND0; Q811R8;
DT   20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   24-JAN-2024, entry version 132.
DE   RecName: Full=Glucose-6-phosphatase 3;
DE            Short=G-6-Pase 3;
DE            Short=G6Pase 3;
DE            EC=3.1.3.9 {ECO:0000269|PubMed:15661744};
DE   AltName: Full=Ubiquitous glucose-6-phosphatase catalytic subunit-related protein;
DE   AltName: Full=glucose-6-phosphatase-beta {ECO:0000303|PubMed:15661744};
DE            Short=Glc-6-Pase-beta {ECO:0000303|PubMed:15661744};
GN   Name=G6pc3; Synonyms=Ugrp;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=CD-1;
RA   Middleditch C., Darakhshan F., Bonnefont J., Guionie O., Burchell A.,
RA   Clottes E.;
RT   "Cloning of a glucose-6-phosphatase catalytic subunit-related sequence
RT   expressed in rodent tissues.";
RL   Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Kidney;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Colon;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=15087461; DOI=10.1074/jbc.m402036200;
RA   Shieh J.-J., Pan C.-J., Mansfield B.C., Chou J.Y.;
RT   "A potential new role for muscle in blood glucose homeostasis.";
RL   J. Biol. Chem. 279:26215-26219(2004).
RN   [6]
RP   IDENTIFICATION, AND TISSUE SPECIFICITY.
RX   PubMed=14765991; DOI=10.1677/jme.0.0320033;
RA   Boustead J.N., Martin C.C., Oeser J.K., Svitek C.A., Hunter S.I.,
RA   Hutton J.C., O'Brien R.M.;
RT   "Identification and characterization of a cDNA and the gene encoding the
RT   mouse ubiquitously expressed glucose-6-phosphatase catalytic subunit-
RT   related protein.";
RL   J. Mol. Endocrinol. 32:33-53(2004).
RN   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP   REGULATION, AND TISSUE SPECIFICITY.
RX   PubMed=15661744; DOI=10.1074/jbc.m410894200;
RA   Ghosh A., Cheung Y.Y., Mansfield B.C., Chou J.Y.;
RT   "Brain contains a functional glucose-6-phosphatase complex capable of
RT   endogenous glucose production.";
RL   J. Biol. Chem. 280:11114-11119(2005).
RN   [8]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=17023421; DOI=10.1074/jbc.m605858200;
RA   Wang Y., Oeser J.K., Yang C., Sarkar S., Hackl S.I., Hasty A.H.,
RA   McGuinness O.P., Paradee W., Hutton J.C., Powell D.R., O'Brien R.M.;
RT   "Deletion of the gene encoding the ubiquitously expressed glucose-6-
RT   phosphatase catalytic subunit-related protein (UGRP)/glucose-6-phosphatase
RT   catalytic subunit-beta results in lowered plasma cholesterol and elevated
RT   glucagon.";
RL   J. Biol. Chem. 281:39982-39989(2006).
RN   [9]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=17318259; DOI=10.1172/jci30443;
RA   Cheung Y.Y., Kim S.Y., Yiu W.H., Pan C.-J., Jun H.-S., Ruef R.A., Lee E.J.,
RA   Westphal H., Mansfield B.C., Chou J.Y.;
RT   "Impaired neutrophil activity and increased susceptibility to bacterial
RT   infection in mice lacking glucose-6-phosphatase-beta.";
RL   J. Clin. Invest. 117:784-793(2007).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Heart, Kidney, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic
CC       reticulum. May form with the glucose-6-phosphate transporter
CC       (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose
CC       production through glycogenolysis and gluconeogenesis. Probably
CC       required for normal neutrophil function. {ECO:0000269|PubMed:15087461,
CC       ECO:0000269|PubMed:15661744, ECO:0000269|PubMed:17023421,
CC       ECO:0000269|PubMed:17318259}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-glucose 6-phosphate + H2O = D-glucose + phosphate;
CC         Xref=Rhea:RHEA:16689, ChEBI:CHEBI:4167, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:61548; EC=3.1.3.9;
CC         Evidence={ECO:0000269|PubMed:15661744};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16690;
CC         Evidence={ECO:0000269|PubMed:15661744};
CC   -!- ACTIVITY REGULATION: Inhibited by vanadate.
CC       {ECO:0000269|PubMed:15661744}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 6.5. {ECO:0000269|PubMed:15661744};
CC       Temperature dependence:
CC         Optimum temperature is 37 degrees Celsius.
CC         {ECO:0000269|PubMed:15661744};
CC   -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC       Multi-pass membrane protein {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in heart and
CC       testis and to a lower extent in spleen, stomach, small intestine,
CC       skeletal muscle and uterus. Expressed in muscle, brain, thymus, lung,
CC       kidney, spleen and pancreas (at protein level). In the brain, expressed
CC       in astrocytes (at protein level) (PubMed:15661744).
CC       {ECO:0000269|PubMed:14765991, ECO:0000269|PubMed:15087461,
CC       ECO:0000269|PubMed:15661744}.
CC   -!- DISRUPTION PHENOTYPE: Mice display reduced glucose-6-phosphate
CC       hydrolytic activity in the brain. No phenotypic difference was noted at
CC       birth but 4 months old female mice display growth retardation. Mutant
CC       mice exhibit a decreased plasma cholesterol concentration and an
CC       increased plasma glucagon concentration but no difference in blood
CC       glucose concentration (PubMed:17023421). Mice display neutropenia and
CC       neutrophil dysfunctions. {ECO:0000269|PubMed:17023421,
CC       ECO:0000269|PubMed:17318259}.
CC   -!- SIMILARITY: Belongs to the glucose-6-phosphatase family. {ECO:0000305}.
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DR   EMBL; AY186239; AAO39164.1; -; mRNA.
DR   EMBL; AK165395; BAE38159.1; -; mRNA.
DR   EMBL; AL954730; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC069959; AAH69959.1; -; mRNA.
DR   CCDS; CCDS25491.1; -.
DR   RefSeq; NP_787949.2; NM_175935.3.
DR   AlphaFoldDB; Q6NSQ9; -.
DR   SMR; Q6NSQ9; -.
DR   STRING; 10090.ENSMUSP00000077995; -.
DR   iPTMnet; Q6NSQ9; -.
DR   PhosphoSitePlus; Q6NSQ9; -.
DR   SwissPalm; Q6NSQ9; -.
DR   EPD; Q6NSQ9; -.
DR   jPOST; Q6NSQ9; -.
DR   MaxQB; Q6NSQ9; -.
DR   PaxDb; 10090-ENSMUSP00000077995; -.
DR   PeptideAtlas; Q6NSQ9; -.
DR   ProteomicsDB; 271628; -.
DR   Pumba; Q6NSQ9; -.
DR   Antibodypedia; 59289; 98 antibodies from 18 providers.
DR   DNASU; 68401; -.
DR   Ensembl; ENSMUST00000070334.10; ENSMUSP00000064276.4; ENSMUSG00000034793.16.
DR   Ensembl; ENSMUST00000078975.8; ENSMUSP00000077995.8; ENSMUSG00000034793.16.
DR   GeneID; 68401; -.
DR   KEGG; mmu:68401; -.
DR   UCSC; uc007lqt.2; mouse.
DR   AGR; MGI:1915651; -.
DR   CTD; 92579; -.
DR   MGI; MGI:1915651; G6pc3.
DR   VEuPathDB; HostDB:ENSMUSG00000034793; -.
DR   eggNOG; ENOG502QS5D; Eukaryota.
DR   GeneTree; ENSGT00950000183150; -.
DR   HOGENOM; CLU_052517_0_0_1; -.
DR   InParanoid; Q6NSQ9; -.
DR   OMA; KKWCSRA; -.
DR   OrthoDB; 4030642at2759; -.
DR   PhylomeDB; Q6NSQ9; -.
DR   TreeFam; TF324388; -.
DR   Reactome; R-MMU-70263; Gluconeogenesis.
DR   UniPathway; UPA00138; -.
DR   BioGRID-ORCS; 68401; 2 hits in 76 CRISPR screens.
DR   ChiTaRS; G6pc3; mouse.
DR   PRO; PR:Q6NSQ9; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; Q6NSQ9; Protein.
DR   Bgee; ENSMUSG00000034793; Expressed in choroid plexus of fourth ventricle and 238 other cell types or tissues.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0004346; F:glucose-6-phosphatase activity; IDA:MGI.
DR   GO; GO:0006094; P:gluconeogenesis; IDA:MGI.
DR   GO; GO:0051156; P:glucose 6-phosphate metabolic process; ISO:MGI.
DR   GO; GO:0015760; P:glucose-6-phosphate transport; IGI:MGI.
DR   CDD; cd03381; PAP2_glucose_6_phosphatase; 1.
DR   Gene3D; 1.20.144.10; Phosphatidic acid phosphatase type 2/haloperoxidase; 1.
DR   InterPro; IPR016275; Glucose-6-phosphatase.
DR   InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf.
DR   InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR   PANTHER; PTHR12591; GLUCOSE-6-PHOSPHATASE; 1.
DR   PANTHER; PTHR12591:SF2; GLUCOSE-6-PHOSPHATASE 3; 1.
DR   Pfam; PF01569; PAP2; 1.
DR   PIRSF; PIRSF000905; Glucose-6-phosphatase; 1.
DR   SMART; SM00014; acidPPc; 1.
DR   SUPFAM; SSF48317; Acid phosphatase/Vanadium-dependent haloperoxidase; 1.
DR   Genevisible; Q6NSQ9; MM.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Gluconeogenesis; Hydrolase; Membrane;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..346
FT                   /note="Glucose-6-phosphatase 3"
FT                   /id="PRO_0000334513"
FT   TOPO_DOM        1..24
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        25..45
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        46..56
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        57..77
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        78..108
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        109..129
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        130..138
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        139..159
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        160..167
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        168..186
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        187..197
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        198..218
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        219..254
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        255..273
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        274..283
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        284..304
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        305..307
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        308..328
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        329..346
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        114
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        167
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   BINDING         79
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255"
FT   BINDING         161
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        136
FT                   /note="R -> Q (in Ref. 2; BAE38159)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        207
FT                   /note="M -> L (in Ref. 1; AAO39164)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   346 AA;  38782 MW;  50CDA634BCABA014 CRC64;
     MESTLSAGII MAEALQNRLP GLENMWLWVT FLGDPKNLFQ FCFPAAYYAS RRLGISVLWI
     TFIAEWLNLV FKWFLFGDRP FWWVHESGYS TQTPIQIHQF PSSCETGPGS PSGHCMITGA
     ALWPVMTAIS SQVASRSRSP WVRVIPGLAY CTFLLAVGLS RVFLLAHFPH QVLGGLIVGA
     ALGWLMSPRV PMERELSFYG LTALALMLGA SLMYWTLFTL GLDLSWSINL ASKWCERPEW
     VHMDSRPFAS LSRDSGSALG LGIALHTPCY AQIRRAHLGN GQKIACFVLA MGLLVFLEWL
     GYPPQISLFY IFNFLKYTLW PCLVLALVPW VVHTLSDQEA PPIRSS
//